Proposed pathways for neutropenia. Excessive stress responses, such as the UPR, ER stress, or reactive oxygen species (ROS), may lead to DNA damage, with or without faulty repair by p53-dependent or p53-independent pathways. These events, in turn, may lead to a subsequent block in differentiation or cell death. Other stressful stimuli include radiation exposure, infections, low nutrient supply, or faulty protein synthesis due to defective ribosome assembly. In other cases, neutropenia may result from defective differentiation and release due to receptor/transcription factor defects in signal transduction.